Cryptococcus

Cryptococci: Organisms
Budding
Encapsulated
Unencapsulated
Ultrastructure
Muscle
Cryptococci
Multifocal involvement
Histiocyte association
Foci (Cryptococcomas)
Perimysium
Capillaries
Muscle fibers
Atrophy
Mitochondrial Δ
Nerve

Muscle MRI: T2

Cryptococcal Myopathy
Patchy involvement of paraspinous muscles

Muscle

Cryptococcus: Multifocal Involvement of Muscle

H&E stain

Pattern of Infection
Multifocal collections of organisms: Small cryptococcomas
Locations: Endomysium & Perimysium
Other cell components: Histiocytes

H&E stain

Cryptococcus: Histiocytic Cell & Cryptococcal foci

Acid phosphatase stain

Pattern of Infection
Histiocytic cells
Associated with cryptococcal clusters
Scattered in endomysium: Probably near capillaries
Locations: Endomysium; Perimysium

Acid phosphatase stain

Acid phosphatase stain

Acid phosphatase: Stains
Cell wall (Rim of cryptococci inside capsule)
Confluent through focus
May obscure cryptococcal organisms
Similar to granulomas associated with foreign bodies or IMAM

Acid phosphatase stain

CD 163 stain

Histiocytic Cells: Distribution
Foci: Present in clusters along with (around) cryptococci
Scattered: In muscle endymysium near capillaries

CD 163 stain

CD 163 stain

Histiocytic Cells: Distribution
Foci: Present in clusters with processes around cryptococci
Cryptococci: Often intacellular within Histiocyte cytoplasm

CD 163 stain

CD 163 stain

Cryptococcal Foci

H&E stain

Cryptococcal foci
Locations
Clusters (foci) occur in: Endomysium or Perimysium
Contents
Some foci contain mainly cryptococci, connective tissue & indistinct cells that stain for acid phosphatase (Above).
A few foci contain clusters of lymphocyte-like cells (Below)
Neighboring muscle fibers
Often smaller than in other areas

H&E stain

Some cryptococcal foci contain clusters of lymphocyte-like cells

Congo red stain

Cryptococcal focus
Fewer cryptococci
More other cells & tissue

H&E stain

Cryptococci: Organisms

Cryptococci: Many budding

H&E stain

H&E stain

Cryptococcus: Organisms
Sizes: Varied
Structure
Peripheral: Clear capsule with varied thickness
Central
Rimmed circular region
A few show budding (Arrows, Below)

H&E stain

Mucicarmine stain

Mucicarmine: Stains cryptococcal organisms

Mucicarmine stain

Mucicarmine stain
From: Wikimedia

Grocott methenamine silver (GMS) stain

Grocott methenamine silver: Stains cryptococcal organisms

Grocott methenamine silver (GMS) stain

PAS stain

Cryptococcus: Organisms
Sizes: Varied
Structure
Peripheral: Clear capsule with varied thickness
Central: Rimmed circular region, PAS+
Clustered in endomysium or perimysium

PAS stain

Cryptococcal cluster: Most organisms in this cluster have thin, or no, capsules

PAS stain

Alcian blue: Stains central region of organisms

Alcian blue stain

Sudan black: Stains round area within central region of some organisms

Sudan stain

Thin layer of connective tissue around cryptococci
Stained by Gomori trichrome

Gomori trichrome stain

Cryptococci contain no mitochondria

COX stain

Cryptococci: Ultrastructure

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

From: R Schmidt

Cryptococcus within a Histiocyte

From: Wikimedia DC/ Carolina Coelho

From: R Schmidt

From: R Schmidt

From: R Schmidt

C_5b-9 deposited on tissue within and surrounding a cryptococcal focus

C_5b-9 stain

Cryptococcal myopathy: Muscle fibers

Gomori trichrome stain

Muscle fibers in cryptococcal myopathy
Diffuse atrophy
Smallest muscle fibers are located at edge of fascicles near cryptococcal focus

VvG stain

Gomori trichrome stain

Muscle fibers in cryptococcal myopathy
Diffuse atrophy
Fiber sizes: Varied

VvG stain

VvG stain

Cryptococcal myopathy
Muscle fibers
Diffuse atrophy
Fiber sizes: Varied
Smaller fibers at edge of fascicle near damaged perimysium
NADH stains small fibers dark (Below)

NADH stain

COX stain

Cryptococcal myopathy: Mitochondrial pathology
Megaconial: Most mitochondria are large
Some COX- muscle fibers are present

COX stain

Type 2 fiber predominance

ATPase pH 4.3 stain

MHC Class I: Upregulated on surface of all muscle fibers

MHC Class I stain

Cryptococcus: Perimysial connective tissue involvement

H&E stain

Cryptococcal foci within perimysial connective tissue
Some foci contain mostly cryptococcal organisms (Above)
A few foci contain cells and cryptococci (Below)